An experimental obesity pill that works in a different way from the wildly popular Ozempic may help people lose weight, according to results from a small, preliminary human trial.
Ozempic and other GLP-1 drugs reduce food intake by stimulating a feeling of fullness. They act on the brain to promote satiety and on the gut to slow the movement of food through the stomach, helping people feel full longer. As a result, people on the drugs lose weight because they eat less.
But a new drug may be able to burn energy, and thus fat, without reducing appetite. In a Phase I trial described today in the journal Nature Metabolism, the drug led to statistically significant weight loss in participants after two weeks. Dubbed SANA, the drug is derived from salicylate, a compound used to make aspirin. Developed by Eolo Pharma of Montevideo, Uruguay, it activates a pathway called creatine-dependent thermogenesis.
Creatine is perhaps best known as a nutritional supplement taken after exercise to help build muscle mass, but the compound also occurs naturally in the human body and is important for energy production.
“It has been known for a long time that creatine has good effects on metabolism,” says Carlos Escande, cofounder and chief scientific officer of Eolo. In the 1970s, researchers found that rats exposed to cold used a lot of creatine. It wasn’t until a decade ago that a Harvard team found that creatine is used in fatty adipose tissue during exposure to cold to generate heat.
The process of burning energy and generating heat to maintain a stable internal temperature is known as thermogenesis. Creatine-dependent thermogenesis refers to how the breaking down of creatine, particularly in fat cells, contributes to this heat and energy production.
“What we have found is that our compound stimulates this creatine-dependent heat production pathway,” Escande says.
In the first part of the trial, Eolo scientists randomly assigned 17 healthy-weight individuals to receive either a placebo or a single pill of SANA at a low, medium, or high dose. At all doses, the drug was safe and well-tolerated with no serious side effects. In the second part of the trial, they tested the drug in 24 participants with obesity for 15 days. Volunteers were randomly sorted into three groups to receive either a placebo or a low, medium, or high dose of SANA twice a day for the length of the study. Each group had six people taking the drug and two on a placebo. During the study period, participants stayed at a clinical facility where they received high-carbohydrate meals.
At the end of the two weeks, the participants taking the highest dose of SANA showed weight loss of about 3 percent, which is comparable to the weight loss seen in people taking Ozempic and Wegovy over the same period of treatment. They were also asked to fill out a questionnaire regarding appetite and satiety, and none reported decreased appetite or satiety.